PHLC_CLOHA
ID PHLC_CLOHA Reviewed; 399 AA.
AC P59026;
DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Phospholipase C;
DE Short=PLC;
DE EC=3.1.4.3;
DE AltName: Full=Beta toxin;
DE AltName: Full=Phosphatidylcholine cholinephosphohydrolase;
DE Flags: Precursor;
GN Name=plc;
OS Clostridium haemolyticum.
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Clostridiaceae;
OC Clostridium.
OX NCBI_TaxID=84025;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=7170;
RX PubMed=16701524; DOI=10.1016/j.anaerobe.2004.04.006;
RA Hauer P.J., Yeary T.J., Rosenbusch R.F.;
RT "Cloning and molecular characterization of the beta toxin (phospholipase C)
RT gene of Clostridium haemolyticum.";
RL Anaerobe 10:243-254(2004).
RN [2]
RP REVIEW.
RX PubMed=11008117; DOI=10.1016/s1286-4579(00)01281-8;
RA Jepson M., Titball R.W.;
RT "Structure and function of clostridial phospholipases C.";
RL Microbes Infect. 2:1277-1284(2000).
CC -!- FUNCTION: Bacterial hemolysins are exotoxins that attack blood cell
CC membranes and cause cell rupture. Binds to eukaryotic membranes where
CC it hydrolyzes phosphatidylcholine, sphingomyelin and
CC phosphatidylethanolamine. The diacylglycerol produced can activate both
CC the arachidonic acid pathway, leading to modulation of the inflammatory
CC response cascade and thrombosis, and protein kinase C, leading to
CC activation of eukaryotic phospholipases and further membrane damage (By
CC similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1,2-diacyl-
CC sn-glycerol + H(+) + phosphocholine; Xref=Rhea:RHEA:10604,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17815,
CC ChEBI:CHEBI:57643, ChEBI:CHEBI:295975; EC=3.1.4.3;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC Note=Binds 3 Ca(2+) ions. {ECO:0000250};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 3 Zn(2+) ions. {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000255|PROSITE-ProRule:PRU00678}.
CC -!- DOMAIN: The protein is composed of 2 domains; the N-terminal domain
CC contains the phospholipase C active site (PLC), in a cleft which is
CC also occupied by the 3 zinc ions. The C-terminal domain is a putative
CC phospholipid-recognition domain, which shows structural homology with
CC phospholipid-binding C2-like domains from a range of eukaryotic
CC proteins. The ability to bind membrane phospholipids in a Ca(2+)
CC dependent manner and toxicity is conferred by this C-terminal domain,
CC which also contributes to the sphingomyelinase activity (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the bacterial zinc-metallophospholipase C
CC family. {ECO:0000255|PROSITE-ProRule:PRU00678}.
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DR EMBL; AF525415; AAM88377.1; -; Genomic_DNA.
DR AlphaFoldDB; P59026; -.
DR SMR; P59026; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0034480; F:phosphatidylcholine phospholipase C activity; IEA:UniProtKB-EC.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0044179; P:hemolysis in another organism; IEA:UniProtKB-KW.
DR CDD; cd11009; Zn_dep_PLPC; 1.
DR Gene3D; 1.10.575.10; -; 1.
DR InterPro; IPR001024; PLAT/LH2_dom.
DR InterPro; IPR036392; PLAT/LH2_dom_sf.
DR InterPro; IPR008947; PLipase_C/P1_nuclease_dom_sf.
DR InterPro; IPR029002; PLPC/GPLD1.
DR InterPro; IPR001531; Zn_PLipaseC.
DR Pfam; PF01477; PLAT; 1.
DR Pfam; PF00882; Zn_dep_PLPC; 1.
DR PRINTS; PR00479; PRPHPHLPASEC.
DR SMART; SM00770; Zn_dep_PLPC; 1.
DR SUPFAM; SSF48537; SSF48537; 1.
DR SUPFAM; SSF49723; SSF49723; 1.
DR PROSITE; PS50095; PLAT; 1.
DR PROSITE; PS00384; PROKAR_ZN_DEPEND_PLPC_1; 1.
DR PROSITE; PS51346; PROKAR_ZN_DEPEND_PLPC_2; 1.
PE 3: Inferred from homology;
KW Calcium; Cytolysis; Hemolysis; Hydrolase; Metal-binding; Secreted; Signal;
KW Toxin; Virulence; Zinc.
FT SIGNAL 1..28
FT /evidence="ECO:0000250"
FT CHAIN 29..399
FT /note="Phospholipase C"
FT /id="PRO_0000023934"
FT DOMAIN 29..277
FT /note="Zn-dependent PLC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00678"
FT DOMAIN 283..399
FT /note="PLAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT REGION 275..282
FT /note="Linker"
FT BINDING 28
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00678"
FT BINDING 38
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00678"
FT BINDING 83
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00678"
FT BINDING 95
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00678"
FT BINDING 153
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00678"
FT BINDING 157
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00678"
FT BINDING 157
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00678"
FT BINDING 163
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00678"
FT BINDING 175
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00678"
FT BINDING 179
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00678"
FT BINDING 298
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 299
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 300
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 320
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 321
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 323
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 324
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 325
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 325
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 363
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
SQ SEQUENCE 399 AA; 45942 MW; 97A8FA5537083BEA CRC64;
MNKKKILKFI CSAVLSFTLF SGYKSYAWDG KVDGTGTHAL IVTQAVEILK NDVISTSPLS
VKENFKILES NLKKLQRGST YPDYDPKAYA LYQDHFWDPD TDNNFTKDSK WYLAYGINET
GESQLRKLFA LAKDEWKKGN YEQATWLLGQ GLHYFGDFHT PYHPSNVTAV DSAGHTKFET
YVEGKKDSYK LHTAGANSVK EFYPTTLQNT NLDNWITEYS RGWAKKAKNM YYAHATMSHS
WKDWEIAATE TMHNVQIGSA GIIYRFLNEV SGTINTTENS KINEIMVVIK TANEDKAGTD
HYIHFGIEAK DGKKYEWTLD NPGNDFEKNQ EDSYRINLKD NKLTLQDIAK TWIRKERGAG
VRDDWKPEYV KVIINSDVKY QANINEWFGD NKTFYINNK
